Magnetic field stimulation

ABSTRACT

A magnetic coil system featuring a multi-layer structure ( 312   a,    312   b ), a spherical shape, or both allows for efficient generation of a gradient magnetic field that induces an electric field in air in a region proximate to the coil. By subjecting at least a portion of a person&#39;s brain to the induced electric field various psychiatric disorders can be treated.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims priority to and benefit of U.S. ProvisionalPatent Application No. 61/539,877 titled “Low Field MagneticStimulation,” filed on Sep. 27, 2011, and U.S. Provisional PatentApplication No. 61/539,893 also titled “Low Field magnetic Stimulation”and filed on Sep. 27, 2011, each of which is incorporated herein byreference in its entirety.

BACKGROUND OF THE INVENTION

The present invention relates generally to a system and method ofinduced electric fields and, more particularly, to a system thatprovides induced electric fields that interact with the brain.

Psychiatric conditions are predominantly treated with pharmaceuticalagents. For example existing treatment approaches for depression inbipolar disorder and in major depressive disorder utilize primarilypharmacologic agents, such as selective serotonin reuptake inhibitorsand other antidepressant drugs. These agents can be of limited efficacyand may have objectionable side effects.

Repetitive transcranial magnetic stimulation (rTMS) has been used withthe goal of treating depression, (see, e.g., George et al., The Journalof Neuropsychiatry and Clinical Neurosciences, 8:373, 1996; Kolbinger etal., Human Psychopharmacology, 10:305, 1995), bipolar disease and otherpsychiatric conditions. The success of rTMS in the treatment ofdepression has been varied and has been described in a recent review as“often statistically significant [but] below the threshold of clinicalusefulness” (see Wassermann E M, Lisanby S H: Therapeutic application ofrepetitive transcranial magnetic stimulation: a review. ClinNeurophysiol2001; 112:1367-1377). Furthermore, rTMS treatment can be unpleasant,with some patients declining participation due to scalp pain induced bythe apparatus (George M S, Nahas Z, Molloy M, Speer A M, Oliver N C, LiX B, Arana G W, Risch S C, Ballenger J C: A controlled trial of dailyleft prefrontal cortex TMS for treating depression. BiolPsychiatry 2000;48:962-970). The rTMS treatment also carries a small risk of seizure(Wassermann EM: Risk and safety of repetitive transcranial magneticstimulation: report and suggested guidelines from the InternationalWorkshop on the Safety of Repetitive Transcranial Magnetic Stimulation,Jun. 5-7, 1996. Electroencephalogr Clin Neurophysiol 1998; 108:1-16).

Alternative techniques have been described for the treatment ofpsychiatric disease using low field strength, high repetition rates, anduniform magnetic gradients (U.S. Pat. Nos. 7,033,312 and 6,572,528, andU.S. patent application Ser. No. 11/580,272). Each of these patents andpatent applications is incorporated herein by reference in its entirety.Time-varying magnetic fields were used for the purpose of enhancingbrain function and for treating various symptoms of depression, anxiety,affective disorders, bi-polar disorder, post-traumatic stress disorder,and obsessive compulsive disorder.

Magnetic fields have also been used in Magnetic Resonance Imaging (MRI)systems. These systems use a coil to generate a magnetic field in air towhich a portion of a subject's body can be exposed for imaging. Atypical MRI coil is a full coil having four elements, such as thatdepicted in FIG. 5. The desired magnetic field is typically produced ina region in the middle of the coil—a region that is approximatelyequidistant from all four elements. Using MRI coils for treatment hasseveral disadvantages, however, as described below.

One significant limitation on the use of an MRI gradient coil is itsphysical size, as imposed by the system, by power concerns, and by thepatient. First, the larger the gradient coil, the larger its inductance,and the more the required power to operate the coil. A big coil usuallyrequires more expensive amplifiers, and may impose power switchingrequirements that cannot be addressed merely by coil design. The portionof the patient which will be imaged must fit inside the coil, whichimposes a lower limit on size. This is a limitation on minimum innerdiameter of the gradient coil.

Second, the MRI coil fits inside the magnet. The cost and the difficultyin engineering required to make magnet both increase with the increaseof the inner diameter of an MRI magnet. A MRI magnet must be largeenough to accommodate a patient and the gradient coil within its innerdiameter. A typical inner diameter of an MRI magnet must be large enough(e.g., about 90 cm) to provide an adequate opening so that the patientcan be located at or near the region where the coil produces the desiredmagnetic field. This places an upper limit on gradient coil outerdiameter.

An MRI gradient coil assembly typically contains 6 elements of gradientcoils, two each for the X, Y and Z magnetic field gradient directions. Agradient coil assembly also usually contains resistive shim coils, andcooling for the resistive heat generated by the different coils. All ofthese items must fit within the inner and outer diameter limits imposedon the coil assembly by the patient access and the magnet size and cost.

In MRI systems, there is a need to cool the resistive heating that isgenerated inside the coil during operation—most systems need to havewater or liquid cooling, because the coil is tightly packed between theinner and outer size limitations. Second, there is magnetic force on thewires in the coil when they have current in them; this causes a netforce, usually in the form of a torque that can cause the coil to move.

In MRI systems, the dynamic magnetic fields are reflected from thesurrounding magnet and would interfere with the desired target magneticgradient fields. To prevent this, each gradient coil {X, Y, Z} isdesigned as a pair of coils—an inner coil and an outer coil—with theouter coil providing an active shield that prevents the gradientmagnetic field from reaching the main MRI magnet. Thus, the outer coilmerely prevents the magnet from interfering with the field produced bythe inner coil.

A gradient coil that only surrounds a patient's head can have a smallerinner diameter, and as a result, may require less power and lesscooling. The standard configuration of an MRI coil (i.e., the full coilhaving four elements as shown in FIG. 5), however, requires a length ofcoil to extend below the imaging area, i.e., the head. Put another way,the head must be positioned in the middle of the coil. Therefore, thecoil must be large enough to accommodate shoulders of the person to betreated. Moreover, typical small-diameter coils do not have a strongmechanical mounting as that of the body coil, and hence, have a greaterrisk of movement from torque. This poses risk of severe patient injury.Finally, even though the MRI coils that have a relatively small diameterrequire less power, they still require cooling systems.

There was an attempt to address the shoulder access problem by severaldesigns proposed in the 1990s. These designs used only a “half-coil”design. In this case, the half-coil reduces the extent of the coil belowthe imaging spot by cutting the coil in half, resulting in reducedgradient field homogeneity but allowing full access to the head, withoutrequiring the person's shoulders to be surrounded by the coil. Such MRIcoils, however, had significant torque and they were not safe forpatient use. Also, the reduced gradient field homogeneity was notadequate for imaging purposes. The various issues relating to the use ofMRI half coils are discussed, for example, in U.S. Pat. No. 5,177,442 toRoemer (describing half coil as having torque (as described by Kondo));U.S. Pat. No. 5,278,504 to Patrick (describing an asymmetric coil whichis not a half coil, in order to eliminate torque); and U.S. Pat. No.5,793,209 to Kondo (classifying certain coils as effective in imagingbut having a torque problem, and certain other coils as effective intorque mitigation but having imaging problems).

Therefore, there is a need for improved apparatuses, systems and methodsfor treatment of brain using electro-magnetic radiation which overcomesthe disadvantages and limitations of the prior MR apparatuses andsystems discussed above.

SUMMARY OF THE INVENTION

Various embodiments of the present invention feature systems for theinduction of electric fields in air. These systems are smaller in sizeand less bulky compared to previously known coils and may generate lessheat. In some embodiments, this is achieved, in part, by employing acoil that has at least one element having two layers, so as to decreasethe overall resistance of the coil, which in turn can decrease the heatgenerated by the coil when compared with conventional coils.Additionally or in the alternative, in some embodiments, the coilincludes only one or two elements that are cylindrical, spherical, flat,or bent in shape. Such a coil can induce the electric field outside theregion enclosed by the coil, such that the patient's head need not besurrounded by the coil, which can increase patient comfort andsimultaneously allows the coil size to be smaller than a coil thatsurrounds the patient's head. Various embodiments also feature a methodof treatment by generating a varying aggregate magnetic field using acoil having one or more elements. The varying magnetic field induces anelectric field in air, and a patient's brain is disposed within theregion in which the field is induced for the treatment of disordersand/or the enhancement of brain function.

The delivery of these induced electric fields fall into the class oflow-field magnetic stimulation (LFMS) techniques. Various embodiments ofcoils according to the present invention avoid one or more of theproblems associated with the MRI coils described above. The inventiondoes not utilize a constant magnetic field, and so there is no magnetsuch as is found in MRI systems and no size limitations imposed by themagnet, nor requirements for torque free design since there is nomagnetic field to provide the torque. Second, the invention requiresonly one gradient field, and so two gradient coils sets and anyresistive shim coils can be eliminated.

The coil module includes a coil and an optional housing for the coil.The coil includes one or more elements, each of which generates amagnetic field that induces a target electric field in air, and asubject's brain can be disposed in the region where the electric fieldis induced. A coil may have one or more elements that are disposed on asingle surface in a non-overlapping manner. Any element may have one,two or more layers to provide reduction of resistive heating as comparedto use of a single element. In one embodiment, the coil has a singleelement that is arranged on a circular or elliptic cylindrical surfacehaving a first radial direction, a second radial direction, and alongitudinal direction. The dimensions of the coil along the first andsecond radial directions may have the same value. Such an embodimentfacilitates relatively easy and/or cheap manufacturing of the coil.

In some embodiments, the coil induces an electric field in a region thatis proximate to the volume enclosed by the coil. This can be achievedusing a half coil design, i.e., using a coil that has two elements. Thisallows the coil size to be smaller than that of an MRI coil. In theregion proximate to the volume enclosed by the coil, the inducedelectric field is not sufficiently homogeneous for imaging in an MRIsystem (e.g., uniformity within 5%-10%), but the homogeneity is adequatefor treatment purposes. The coil elements in such a coil can have asurface that is cylindrical, spherical, rectangular, flat, or bent inshape. In various embodiments the coil does not need liquid cooling. Insome embodiments, a coil element includes two or more layers ofconductors, further decreasing the heat generated by the coil.

Accordingly, in one aspect embodiments of the present invention featurea system for efficiently inducing an electric field. The system includesa pulse generator and a magnetic coil. The magnetic coil has at leastone element (e.g., a first element). The first element includes at leasttwo layers—a first layer having an interior surface and an exteriorsurface, and a second layer having an interior surface and an exteriorsurface such that the interior surface of the second layer is separatedfrom the exterior surface of the first layer by a distance. The firstand second layers are in electrical communication with the pulsegenerator and are adapted to produce respective first and secondmagnetic fields. The first and second layers are positioned such thatthe first and second magnetic fields combine to produce an aggregatemagnetic field having a field strength greater than either the first orsecond magnetic field.

In some embodiments, the distance between all points of the interiorsurface of the second layer and all corresponding points of the exteriorsurface of the first layer is within a tolerance threshold. Thetolerance threshold, for example, may be about 25% or 10% or 5% of amedian distance between the two surfaces. In some embodiments, thedistance between the first and second layers is less than about 5millimeters. The interior surface of the first element may be either acurved surface or a segmented surface having at least two segments at anangle with respect to one another. The first layer of the first elementmay include a pattern cut in a metal surface or wound wire. The woundwire can be a solid wire, a stranded wire, or a stranded, insulated litzwire. The first layer of the first element may include a number of turnsof a conductor, such as a wound wire or a pattern cut in a metalsurface. At least one pair of adjacent turns of the conductor may bespaced apart and the several turns may be distributed over the entirefirst layer. In some embodiments, the distance between the two layers isselected such that the aggregate magnetic field is produced in a regionproximate to the magnetic coil. In addition, or alternatively, the firstand second layers may be configured such that each layer generates lessthan about 50 W of heat.

In some embodiments, the first element includes a third layer having aninterior surface and an exterior surface, and the interior surface ofthe third layer is separated from the exterior surface of the secondlayer by a distance. The third layer produces a third magnetic fieldthat combines with the first and second magnetic fields to produce anaggregate magnetic field having a field strength greater than theaggregate magnetic field produced by the first and second magneticfields.

The magnetic coil may also include a second element such that an innersurface of the second element and the inner surface of the first elementform separate portions of a single surface. In some embodiments, thesingle surface is the outer surface of a cylinder having a diameter ofabout 14 inches, and the second element includes two layers. Each of thefirst and second layers of the first element, and each of the two layersof the second element include a spiral pattern.

One embodiment features a method of treating a psychiatric disorder orenhancing brain function using the system having a two-layer coilelement, described above. The method includes supplying electric powerto the magnetic coil via the pulse generator so as to produce theaggregate magnetic field. The aggregate magnetic field may induce anelectric field in air proximate to the coil. The method also includesdisposing a subject relative to the magnetic coil such that at least aportion of the subject's head is located in a region where the electricfield is induced. The psychiatric disorder may include one or more ofmood disorder, depression, stress and anxiety, schizophrenia,post-traumatic stress disorder (PTSD), and obsessive-compulsive disorder(OCD). The subject may be disposed in either a supine position or aseated position.

In another aspect, various embodiments of the present invention featurea system that can improve patient comfort. The system includes a pulsegenerator and a magnetic coil. The magnetic coil has a first element andan inner surface of the first element forms at least a part of aspherical surface. The first element is in electrical communication withthe pulse generator. A parameter of the magnetic coil may be selectedsuch that the coil produces a gradient magnetic field proximate to aregion at least partially enclosed by the spherical surface. Theparameter is selected such that the gradient magnetic field can inducean electric field in air up to about 50 V/m. The coil parameter may beone of a radius of the spherical surface, a polar angle of a coilsegment, and an azimuth angle of the coil segment.

In some embodiments, the magnetic coil includes a second element, and aninner surface of the second element and the inner surface of the firstelement form separate portions of the spherical surface. The firstelement may include a first layer having an interior surface and anexterior surface, and a second layer having an interior surface and anexterior surface. The interior surface of the second layer may beseparated from the exterior surface of the first layer by a distance.The distance between all points of the interior surface of the secondlayer and all corresponding points of the exterior surface of the firstlayer may be within a tolerance threshold. The tolerance threshold, forexample, may be about 25% or 10% or 5% of a median distance between thetwo surfaces. In some embodiments, the first element includes a numberof turns of a conductor, such as a wound wire or a pattern cut in ametal surface. At least one pair of adjacent turns of the conductor maybe spaced apart and the several turns may be distributed over the entirefirst element.

One embodiment features a method of treating a psychiatric disorder orenhancing brain function using the system in which the inner surface ofthe first element forms at least a part of a spherical surface, asdescribed above. The method includes supplying electric power to themagnetic coil via the pulse generator so as to produce the aggregatemagnetic field. The aggregate magnetic field may induce an electricfield in air proximate to the coil. The method also includes disposing asubject relative to the magnetic coil such that at least a portion ofthe subject's head is located in a region where the electric field isinduced. The psychiatric disorder may include one or more of mooddisorder, depression, stress and anxiety, schizophrenia, PTSD, and OCD.The subject may be disposed in either a supine position or a seatedposition.

In another aspect, various embodiments of the present invention featurea method of treatment using an induced an electric field. The methodincludes controlling a pulse generator during a first interval toproduce a gradient magnetic field using a coil. The gradient magneticfield has a magnitude that increases at a first rate during the firstinterval. The pulse generator is controlled during a second intervalthat is substantially longer than the first interval, such that themagnitude of the magnetic field decreases during the second interval ata second rate substantially smaller than the first rate. As such, anelectric field having a magnitude greater than zero is induced in airduring the first interval and an electric field of a negative magnitudeis induced in air during the second interval. The pulse generator iscontrolled such that an electric field integrated over a periodcomprising the first and second intervals is substantially zero. Theabove steps may be repeated alternately. The method also includesdisposing a subject relative to the coil such that at least a portion ofthe subject's head is located in a region where the electric field isinduced. A repetition of the electric field having a magnitude greaterthan zero may form a series of electric field pulses. A frequency ofthat series of pulses may be at least 100 Hz.

In some embodiments, the portion of the subject's brain that is locatedin the region where the electric field is induced includes at least aportion of cortical surface of the subject's brain. The treatment mayinclude enhancing brain function or treating a psychiatric disorder, andthe psychiatric disorder can be one or more of mood disorder,depression, stress and anxiety, schizophrenia, PTSD, and OCD. Thesubject may be disposed in either a supine position or a seatedposition.

In another aspect, various embodiments of the present invention featurea method of treatment using an induced electric field. The methodincludes controlling a pulse generator during a first interval toproduce a gradient magnetic field using a coil. The pulse generator iscontrolled such that the gradient magnetic field induces severalconsecutive sinusoidal electrical pulses having substantially constantamplitude in air during the first interval. The pulse generator iscontrolled during a second interval such that the gradient magneticfield induces an electric field of substantially zero magnitude in airduring the second interval. These steps are repeated in an alternatingmanner. The method also includes disposing a subject relative to thecoil such that at least a portion of the subject's head is located in aregion where the several consecutive sinusoidal pulses are induced. Afrequency of the consecutive sinusoidal pulses may be greater than about100 Hz.

The subject may be disposed relative to the coil such that at least aportion of cortical surface of the subject's brain is located in aregion where the sequence of sinusoidal pulses is induced. In someembodiments, the treatment includes enhancing brain function or treatinga psychiatric disorder. The psychiatric disorder may include one or moreof mood disorder, depression, stress and anxiety, schizophrenia, PTSD,and OCD. The subject may be disposed in either a supine position or aseated position.

BRIEF DESCRIPTION OF THE DRAWINGS

The drawings illustrate embodiments presently contemplated for carryingout the invention. In the drawings:

FIG. 1 is a schematic showing the components of the system;

FIG. 2 shows an optional cylindrical structure for supporting coilelements;

FIGS. 3A-3G schematically illustrate various embodiments of two-layercoils;

FIG. 4 shows an envelope function graph;

FIG. 5 shows a full coil (e.g., a coil having four elements);

FIG. 6 shows a half coil (e.g., with only two coil elements);

FIG. 7 shows a quarter coil (e.g., with only one coil element);

FIGS. 8A-8C depict coil elements disposed in a substantially sphericalarrangement;

FIGS. 9A-9C depict coil elements disposed in a substantially flatarrangement;

FIG. 10 depicts a coil element disposed in a bent arrangement;

FIG. 11 shows a square pulse pattern with 3 bursts of 12 square pulseseach;

FIG. 12 depicts a “zero net integral” pulse pattern; and

FIG. 13 shows a pulse pattern with 3 bursts of 12 sine pulses each.

DESCRIPTION OF PREFERRED EMBODIMENTS

A device 10 according to an embodiment of the present invention is shownin FIG. 1. The device 10 has a magnetic coil module 12, an amplifier 14,and a waveform generator 16. The waveform generator 16 (e.g., ageneral-purpose programmable computer or a purpose-built electriccircuit) provides an electrical pulse sequence to the amplifier 14,which amplifies the electrical signals and provides them to the magneticcoil 12. The coil 12 produces a magnetic field in response to theelectrical signals received from the amplifier 14. If the electricalsignals vary in time, the magnetic field typically induces an electricfield in air.

The coil module in various embodiments of an LFMS device according tothe present invention includes a coil and a housing for the coil. Thecoil includes one or more elements, each of which generates a magneticfield that may induce a target electric field in air, and a subject'sbrain can be disposed in the region where the electric field is induced.Typically, the coil has one or more elements that are disposed in anon-overlapping manner, but in some embodiments the elements are locatedwith respect to each other such that they partially overlap. FIG. 2depicts a structure 200 over or within which the elements of themagnetic coil may be disposed. The structure 200 is a cylinder and hasfirst and second radial directions 202, 204, respectively, and alongitudinal direction 206. A magnetic field may be produced in whichany vector component of that field may be produced with a lineargradient in one of these three directions, provided that the remainingvector components of the field satisfy Maxwell's equations. Thestructure 200 may have other shapes (e.g., spherical, ellipsoidal,etc.), and it may even be flat. In fact, the structure 200 is optional,i.e., the coil elements may be configured to form a magnetic coilwithout using a separate structure upon which those elements aredisposed.

Reducing Heat Dissipation Using a Multi-Layer Coil

The coils in various embodiments may use a significant amount ofelectrical current in order to provide the required magnetic field. Thecoil in each of these embodiments will undergo resistive heating duringoperation, and the coil will increase in temperature until the heat lostthrough cooling equals the heat generated during operation. Because thecoil is in close proximity to the patient during device operation,heating must be limited for patient comfort and safety. In addition,reducing heat generation by the coil allows for a wider range ofmaterials to be used as part of the coil and coil housing due to thelower operating temperature, facilitating easier and less expensivemanufacturing.

Cooling is performed through conductive means (radiative cooling at roomtemperature is not significant). Typical cooling methods for aconventional coil include liquid cooling or air cooling. Liquid coolingis very effective but adds system cost, maintenance cost, and the riskof on-site malfunction to the device. Air cooling requires no additionalcost or subsystem but is limited to the order of 60 W power levels (a 60W light bulb level, for example, scaled by surface area).

Heating in a magnetic coil is given by Î2*R, where I is the root meansquare current and R is the resistance of the device (at the frequencyof operation). While the operating current I will be constrained by therequired magnetic field for a given coil, the resistance may be alteredin order to control heating. The most direct way to reduce heating is touse a conductor with a larger cross sectional area, which will reducethe resistance. The problem with using just a larger cross sectionconductor, however, is that a single conductor having a large crosssection is difficult to use in fabrication of the coil as it isdifficult to bend and form such a conductor without damage. Using alarger cross section conductor also has the disadvantages of requiringmore space and inhibiting portability. Coils that have a dense coverageof conductor on a physical surface may be constrained in the enlargementof conductor along the surface; coils that use particular manufacturingmethods or materials may be constrained in the enlargement of theconductor perpendicular to the surface.

In general, the resistance of a coil made of wire or cable will belimited if larger wires cannot be selected because of pattern density onthe coil winding surface, and because wires have generally similar crosssectional radii in all directions, that will limit the wire sizeperpendicular to the surface. In another example, coils that are madefrom copper sheets (in which a conductive path has been cut) can bedesigned to use as much of the surface as possible for conductor size,but will be constrained as to the thickness of the copper because ofradial bending and other manufacturing limitations. In both cases acoil, wound on a surface, may be limited with respect to the minimumresistance that can be achieved.

In accordance with the present invention, this limitation can beovercome by structuring the coil in multiple layers. In one embodiment,two layers are placed substantially in parallel with respect to eachother, and the two layers generate substantially the same magneticfield. The two coil layers can be connected electrically in series or inparallel as best suits the drive power available in the system. Becausethe fields of the two coil layers can reinforce each other, each of thetwo layers can be driven by ½ the current required to generatesubstantially the same magnetic field using a conventional, single-layercoil. The magnetic fields produced by the individual layers aggregate soas to produce the desired magnetic field. In this case the heatgenerated by the coil (i.e., by the two layers together) is reduced byhalf [(I/2)̂2*R+(I/2)̂2*R)=Î2 R/2]. This offers a substantial improvementin heat reduction. The use of two layers can reduce the heat generatedby a coil in half, and the use of more layers would have a correspondingreduction in heat generated by the device. Various embodiments of theLFMS device generate 13 W of power, using two layers. Because of thislow level of heat, these embodiments do not require a cooling system.This design is well suited for use in treatments in which a significantamount of heat, e.g., 100 W, may be generated without using a two-layercoil.

The use of double layers in a coil allows for two methods of connectingthe coils in a circuit—in parallel electrical connection or serieselectrical connection—in order to share a single power source. Becausethe coil layers are adjacent to each other and provide the same shape offield, there is some choice available in design that can be used toreduce costs or improve performance, in terms of the power requirements.A magnetic coil is substantially an inductor, and can provide a givenmagnetic field using an amount of current. Electric circuit theoryinforms us that the rate of change in current, multiplied by theinductance, determines the required driving voltage. This rule appliesto the inductive voltage; there is an additional term depending on thecurrent that describes the resistance.

For LFMS, the rate of change of the magnetic field, scales the electricfield strength induced by the coil. The magnetic field is proportionalto the electric current. As a result the required rate of change of theelectric current directly affects system design. Electric field theoryalso informs us that for a given continuous current density design for acoil, the inductance increases as the square of the number of “turns” ofwire used to approximate the required continuous current density(“turns” in the sense of the density of discrete conductors,perpendicular to the current direction, that are used to approximate acontinuous current density). When two layer patterns that are similarare placed together and connected, their net inductance includes anadditional interaction term usually equal to twice the mutual inductanceof the two patterns, which is about the sum of the inductances of twolayers. Finally, electric circuit theory informs us that the current ina coil that is required to produce a given field is inverselyproportional to the number of “turns” used in the implementation of thecontinuous design.

Thus, for a single layer coil, halving the number of turns used indesign will double the required current and cut the required voltage by½ (a factor of ¼ for the change in number of turns but a factor of twofor the double rate of change in current from doubled peak current). Ifa second layer is added in series, with the same number of turns as thefirst layer, then the fields of the two layers will add. This means thatin order to achieve the same field as with one layer, each layer can usehalf the current and double the voltage as a single coil. This isequivalent to the original single layer but a double layer coil allows areduced resistance and a freedom to choose the power configuration.

The second layer can be configured in parallel with the first layer toproduce a coil that has the same total current and voltage requirementsas a single layer coil producing substantially the same magnetic field,but with reduced heating because the current in each of the two layersis about half the total current. It can also be configured in series.Either configuration may be advantageous for power supply choice andcost and will depend on available amplifier choices, and therequirements of the LFMS system.

Structure of a Two-Layer Coil

In general, the coil preferably includes a casing and conductor formingthe coil winding. The coil may also include a bonding agent. In oneembodiment the conductor is solid wire. The conductor may also bestranded wire or litz-wound wire. In another embodiment the conductor isa cut solid copper plate, using for example water jet or mechanicallycutting techniques, which may be curved for ease of construction. Thecopper plate may be disposed on a substrate, such as plastic or, e.g.,an FR4 substrate. The casing encompasses the conductor.

In one embodiment, the LFMS system is based on a magnetic coil mountedin a coil assembly and driven by an amplifier; the amplifier waveform iscontrolled by a controller which is in turn run by a computer program ona computer.

With reference to the embodiments illustrated in FIGS. 3A-3G, a coilassembly is based on a 14 inch diameter plastic cylinder 102 which isabout 19 inches long. The plastic cylinder 302 is the mounting surface304 for the coil 300 that includes four copper plates 306 a-306 d. Eachcopper plate is about ⅛ inch thick, and has a spiral cut 308 madetherein, as shown in FIG. 3E. The spiral cut 308 may extend to the edgeof the plate 306 a. The four copper plates form two elements 310 a, 310b of the coil 300; each element includes two plates. In the firstelement, one copper plate is placed on the surface 304 of the plasticcylinder 302, forming the first layer 312 a of the first element 110 a.Another plate is placed on top of the first layer 312 a, forming thesecond layer 312 b of the first element. The first layer 312 a has aninterior surface in contact with the surface 302 and an exteriorsurface. The second layer 312 b also has an interior surface and anexterior surface, and the interior surface of the second layer isseparated from the exterior surface of the first layer by a distance, asdescribed below.

The first and the second layers (e.g., plates or wound wires) arealigned with each other, i.e., the two layers are of about the same sizeand shape and the second layer substantially overlaps the first layer,as illustrated in FIGS. 3B and 3D. In some embodiments, however, thearea of one of the two layers may be larger than that of the other.Alternatively, or in addition, the shapes of the two layers may bedifferent (e.g., layer one may be rectangular and layer two may beovular). In some embodiments, the layers may only partially overlap witheach other, i.e., they may be aligned with an offset, as shown in FIG.3C.

In some embodiments, the plates (layers, in general) are not disposed ona mounting surface such as the surface 304 of the plastic cylinder 302.The inner surfaces of the coil elements, however, form portions of asingle surface. A cross-section of that single surface, as depicted inFIG. 3F, includes an arc 314 corresponding to the one or more coilelements 310 a, 310 b. A distance “d” between two ends 316 a, 316 b ofthe arc 314 is in the range of about 5 inches up to about 36 inches.This enables subjecting a person's head or a portion thereof to anelectric field induced by the coil 300. In some embodiments, the innersurfaces of the coil elements form portions of different surfaces thatare spaced apart by a substantially constant distance.

Each plate (i.e., layer) in each coil element is preferably mounted on asubstrate 314 that serves as a mechanical mount and as an electricalinsulator between the coil windings and any adjacent objects. A spacerin addition to or instead of the substrate 314 may also be used. Thecopper plates are not planar; instead, they have a curved surface asdepicted in FIGS. 3B-3D, such that the surface of the plastic cylinder302 and the two plates are nearly concentric. The thickness of thesubstrate 314, or spacer, or both typically determine the distancebetween the layers 312 a, 312 b such that the use of a 1/16 inch thickFR4 substrate, in accordance with one embodiment, results in a 1/16 inchdistance between these layers. This distance is preferably substantiallyconstant. In other embodiments, the distance can be about 5 mm, 1 cm,etc. The distance between the two layers need not be substantiallyconstant; instead it may vary with a tolerance of about 5%, 10%, 25%,etc. In various embodiments, materials other than FR4, such as anyflexible insulator (e.g., polyester, polyamide, etc.) may be used as asubstrate. In some embodiments, a combination of various materials maybe used while in yet other embodiments, each layer may be separated byair alone.

As also illustrated in FIG. 3G, in some embodiments, instead of usingone plate as a layer of a coil element, the layer is formed using two ormore segments 316 a-316 c, i.e., planar or curved segments, that aredisposed at an angle with respect to each other. Specifically, a surfacenormal 318 a of one layer segment 316 is not parallel to a surfacenormal 318 b of another layer segment 316; instead, the two surfacenormals 318 are at an angle α with respect to each other. For example,the coil element shown in FIG. 10 includes two rectangular segments atan angle. The angle between two segments is generally 45° up to 180°,but segments at an angle less than 45° are also contemplated. Each ofthe segments 316 a-316 c in a layer includes coil windings disposedthereon or spiral cuts made therein. The size and shape of the segmentsand the angles are selected such that the distance between thecorresponding segments of two layers of a coil element (e.g., segments316 a and 320 a, 316 b and 320 b, and 316 c and 320 c) is substantiallyconstant, as shown in FIG. 3G. A cross section of the segmented surfacethus formed is a segmented arc 322. The distance “d” between two ends ofthe arc 322 is in the range from about 5 inches up to about 36 inches.

A spiral cut in each plate forms a coil winding in each layer, having aninner and outer connection; there are about 35 winding turns in eachspiral cut. In general, the number of winding turns is determined by thecurrent density that is required to produce the target field and by thechoice of power source to be used to drive the coil. A given currentdensity can be provided by a high number of turns with a smaller currentor by a lower number of turns with a higher current. In each case thevoltage required of the power source changes to reflect the current andthe coil impedance. High and lower numbers of turns result in higher andlower (respectively) inductance. The resistance of a coil depends onseveral factors; for a wire coil, more turns means a longer wire(increased resistance) and perhaps an upper limit to wire size (in thecase of tightly spaced turns). In a copper plate coil the same factorsapply, with the exception that the resistance will reduce with thenumber of turns directly due to the fact that the entire turn-to-turnspacing will be filled with copper. Thus a design choice in the numberof turns can be made to accommodate different power sources andconductors. A different concern in selecting the number of turns is theuniformity and smoothness of the fields. In general, the spacing can bechosen to be less than the distance between the coil and the head of asubject, so that the magnetic field in the region in which the head isdisposed does not vary greatly. Thus, the choice of the number of turnsmay also be influenced by a requirement for smooth fields. The secondelement of the coil is formed similarly as the first element. The twoelements together span about 180 degrees, i.e., about half thecircumference of a cross section of the plastic cylinder 302, and thelength of the copper plates 306 a-306 d, which is also the length ofeach element, is about 14 inches. Smooth fields may be desired in orderto induce similar magnitude of electric fields throughout regions of thebrain, rather than focusing the fields in one localized portion of thebrain, in order to efficiently provide treatment to these brain regions.

The relative direction of currents in each coil element determines thedistribution of the fields. This direction may be described usingvectors. A positively rotating current (right hand current) is one thatrotates counterclockwise when viewed in a direction against the outwardnormal of the surface. A negatively rotating current (left hand current)has the opposite rotation, clockwise when viewed against the outwardnormal of the surface. Using this vector terminology, coil elements ofthis coil design that are adjacent in either azimuth or in longitudinalposition have the opposite polarity. This corresponds to the approximatecurrent density solution presented above.

The plates (i.e., layers) can have any suitable planar shape such as asquare, rectangle, circle, oval, etc. As described above, the layer canbe planar or may have a curved surface. In one embodiment, the plates312 a-312 d are 21 inches long and 19 inches wide. The two-element coil300 can be used to treat the entire brain of a human subject, but layershaving smaller dimensions can be used if only a portion of the brain orhead is to be treated.

The exact pattern of the spiral cut is determined based in part on amathematical design so that current supplied to the spiral of each layerproduces a magnetic field with a desired spatial distribution, i.e., the“target field.” The coil layers are driven by electrical currentsimultaneously, and the magnetic fields from each layer add to form afinal target field.

The electrical interconnection and rotational directions of the spiralcut in each of the four layers are configured in order to provide amechanically robust assembly and to reduce peak voltages and electricfields between the coil layers and elements. Each spiral cut forms aninner end/connection and an outer end/connection. The rotationaldirection of the current in each element is determined by the desiredtarget field. The spiral direction of the conductor in a layer typicallydepends on the rotational direction of the current and on theconfiguration of connections to the spiral (i.e. current into the inneror outer connection).

In one embodiment, the spiral cuts of the first layer of each elementrotate in a clockwise direction, as viewed from outside the cylinder,traveling outward from the center. The spiral cuts of the two outerplates, i.e., the second layer in each element, are counterclockwisewhen observed in the same manner. In each coil element, the center ofthe plate that forms the first layer is electrically connected to thecenter of the adjacent plate forming the second layer of that element.The outer ends/connections of the second layers in each coil element areconnected together with a wire/bus bar. The outer ends/connections ofthe plates forming the respective first layers in each coil element areconnected to the power source. The centers of the plates are located onthe sides of the cylinder. Thus, all plates are electrically connectedin series, and the current flows as follows: in the first element,current enters from the outer end of the first-layer plate and travelsto the center; connects to the center of second-layer plate and travelsto the outside of the spiral through the outer end of the second-layerplate to the bus bar. From the bus bar, the current enters the secondelement from the outer end of the plate forming the second layer in thesecond element; to the center of that layer; then to the center of theplate forming the first layer, and then through the spiral to the outerend of plate forming the first layer (in the second element), and backto the power supply via the amplifier. This connection and spiraldirection scheme results in a constructive addition of the fields fromthe first and second layers of each element, and enables the reductionin heat generated, through the use of the two adjacent layers and thereduced electrical resistance that they afford.

The current drive for the coils is provided by a standard audiofrequency amplifier, either linear, switching, or other suitable design.The amplifier is controlled by a waveform that is supplied by acontroller. This controller may take the form of a output card mountedin a standard computer that plays a pre-recorded waveform, or it couldbe the output of a special sequencing card such as the Arduino thatplays and repeats segments of the full waveform. In other embodiments,the two layers may be electrically connected in parallel and/or the twocoil elements may be electrically connected in parallel. In embodimentshaving more than two layers and/or more than two coil elements, variouscombinations of series and parallel connections that minimize the heatgenerated by the coil while producing the desired magnetic field arefeasible, and are contemplated.

The amplifier may be driven in current mode or in voltage mode forreasons of electrical safety; in the case of a voltage mode drive,standard pre-emphasis modifications to the desired waveform may beperformed to accommodate the impedance of the coil.

FIG. 4 depicts a typical envelope function used to modulate the targetfield spatially, in the longitudinal direction as shown in FIG. 2, inorder for the target field method to produce finite and practicalelectromagnetic fields. FIG. 5 shows a four element coil. The symmetryof the coil in azimuth and along the z direction results in a coil withfour independent coil elements, each of a spiral form that spans between90 degrees and 180 degrees of the circumference of the coil. The coilelements may be connected in series, parallel or combinations thereof.The number of turns in each coil element may be varied as long as thetotal current crossing each unit length of the surface remains the same(i.e., halving the turns requires doubling the current per turn).

In an LFMS system using a half coil, in which the envelope function istruncated, only one d1 and d2 parameter set (shown in FIG. 4) isimplemented. The d1 and d2 parameters are set to be equal at the radiusof the half coil (about 7 inches) in order to optimize the fieldstrength. A substantially shorter coil for this radius would result in aweaker field, and would require a denser wire pattern, due to themathematical requirements of projecting target fields into space (see “Atarget field approach to optimal coil design,” R. Turner J. Phys. D:Appl. Phys. 19 L147 (1986)). A much longer coil would provide asatisfactory field but would have an unnecessarily large inductance,requiring unnecessary amounts of power for the system. The aspect ratioof length˜diameter is an optimum ratio that balances these concerns.

In one embodiment, the radius of the coil is 14 inches, a size that willaccommodate the patient's head comfortably, and with enough room thatthe field of vision for the subjects is not impeded when the head isplaced in the treatment position, at the end of the coil. This aids inpatient comfort during treatment.

The target field region is an area wherein the magnetic fields exist toinduce the desired electric fields in the subject. The target fieldregion of the coil in FIG. 5 is in the center of the coil, defined as avolume centered at the intersection of the first and second radialdirections of the coil cylinder (e.g., the first and second radii 202,204 in FIG. 2), and in the plane separating the elements longitudinally.

FIG. 6 shows a half coil with only two coil elements. A full coil,described with reference to FIG. 5, has four elements. This coil willhave substantially similar target treatment regions at the end planes ofthe coil elements, providing a coil which is shorter and more patientfriendly. The shorter coil allows subjects to have only a portion oftheir heads enclosed by the coil rather than having the coil positionedon their shoulders. This may relieve symptoms of claustrophobia or othersubject discomfort caused by limited vision or confinement. This mayhave particular value in treating depressed subjects.

FIG. 7 shows a quarter coil with only one coil element. This coil willhave even more substantial deviation from the ideal target field, butthe basic symmetry is still present in the resultant field and issufficient for LFMS.

In one embodiment the coil includes elements that are oriented such thatthe axis of the loop components is along a horizontal direction,collinear with the axis of the coil (also referred to as the Xdirection). In another embodiment, the coil is rotated about the axis ofthe cylindrical form so that the axis of the loop elements is verticaland orthogonal to the X direction (also referred to as the Y direction).In this way the distribution and direction of the fields of the coil arerotated about the axis of the cylindrical form. Coils providingequivalent fields may be constructed using spherical or semi-sphericalboundaries.

In some embodiments, the electric field induced by the magnetic field ofthe coil has substantially uniform field strength over a region in air,having an area of at least about 2 cm², e.g., 4 cm². A person receivingtreatment may be disposed relative to the coil such that at least a partof the cortical surface of the person's brain is located in that regionwhere there electric field strength is substantially uniform. Such anelectric field may be induced using a coil having broadly distributedcoil windings, e.g., windings that have a regular distribution over thearea of the cortex to be treated. If the cortex is 3 cm away from thecoil, a guide is that the wires should be spaced less than 3 cm apart,over the target area, in order to provide uniform electric field overthe area subtended by the coil area.

The optional housing for the coil is made of a non-conductive,insulating material, such as plastic, wood, fiberglass or carbon fiber.In an alternative embodiment the portion of the housing that is notbetween the subject and the coil can be made of a conductive material,such as copper, in order to provide an electromagnetic shielding layerto contain the external field of the device. The housing encompasses thecoil providing protection for the coil, subject and users of the coil.

Some embodiments of the LFMS system include an extra feature, inaddition to the half-coil design and projected target field area, thatprovide for patient comfort. For example, the coil is mounted on asliding platform. This allows a patient to place his or her head on ahead rest while the coil is several inches away—avoiding the possibilityof hitting the head while positioning. After the patient is comfortable,the coil is slid into place. The head of the patient is inside only thefirst few inches of the coil, which may provide a significant reductionin patient anxiety. The coil of the LFMS device can be mounted on amovable platform because the coil generates the required magnetic fieldindependently of a magnet, and hence, need not be located inside amagnet or affixed thereto.

Coil Design Based on the Target Field Method

The target field method (see “A target field approach to optimal coildesign,” R. Turner J. Phys. D: Appl. Phys. 19 L147 (1986)) is a methodof determining the physical location of a set of electrical conductorsso that a desired magnetic or electric field will be produced whencurrent is run through them. This method is used to design MRI gradientand shim coils and any other coils that require fields with a specificfield distribution.

The basic properties of electromagnetic fields are employed to generatesuch fields in a variety of ways. In particular, the fields within aclosed volume may be generated by a larger number of current patternsoutside the volume. These current patterns are chosen to occur ondesired geometric surfaces, such as planes, cylinders, spheres, or othersurfaces of other shapes. Given a surface, and a target field, thecurrent on the given surface that will produce the given target fieldcan be uniquely defined.

Some surface shapes are more suited for use as surfaces for current thatmay produce a desired target field. A surface that fully encloses atarget field volume can most easily produce that target field (withrespect to maximum current density values and amount of stored fieldenergy). The lesser a target field area enclosed by the current bearingsurface, the more difficult the required current pattern (with respectto maximum current density magnitude and amount of stored energy) togenerate that target field. But in general a variety of coil shapes areused to provide a desired target field that exists near the coil,outside the enclosed volume of the coil. A spherical target field, forexample, can be obtained by currents on a cylinder, on a half cylinder,on a sphere, on portions of a sphere, or on planes and plane segmentsnear the target field.

In general practice target fields are defined to exist inside animplicit finite volume enclosed by the coil generating the field. Whilean unbounded extension of the target field outside the enclosed volumetypically results in an impractical current density (with respect tomaximum current density values and amount of stored energy), a practicaldesign is feasible by allowing the field to tend to zero outside theenclosed volume as quickly as possible. Thus, the field achieved by acoil with the actual target region (which is outside the enclosed volumeof the coil) may differ from the specified field (which defines thefiled to be inside the enclosed volume) used for the coil design. Thedegree to which the achieved and specified fields may differ isdetermined by the needs of the particular application. For example, a10% difference is significant for MRI gradient coils; for brainstimulation, however, a 25% change in target field can be tolerated,because the induced electric fields themselves generally changeaccording to the properties of a subject's head.

Therefore, in various embodiments, the coil may include two or moreelements, each of which is preferably disposed in a non-overlappingmanner on a single surface, or in partially overlapping manner onsubstantially concentric surfaces that are spaced apart. The single orthe substantially parallel surfaces may be partially spherical,elliptical, arched, curved, straight (i.e., flat), or bent. As describedherein, “disposed on a surface” means a coil element disposedsubstantially in contact with the surface such that the coil element hasabout the same shape as that of the surface upon which the coil elementis disposed. The coil element may be directly in contact with thesurface or another material such as a substrate may intervene betweenthe surface and the coil element.

In one embodiment, the coil is constructed from a single conductorelement having a single layer. In an alternative embodiment the coil isconstructed from two or more conductor layers as described above. Theseconductors may be electrically connected in series or in parallel. Asstated above, the conductors may be formed using a wound solid cable ora wound stranded cable. The conductor may also be formed by carving apattern in a metal plate or film. The multiple layers may be able toreduce power consumption and cooling requirements of the coil.

The target electric field may extend over the entire brain or regionswithin the brain. In one embodiment, the target electric fields mayaffect the cortical areas of the brain that regulate mood and behavior,such as frontal regions. In another embodiment the target electric fieldmay affect subcortical areas of the brain that regulate mood andbehavior, such as the basal ganglia and thalamus.

The electric field outside of the coil's enclosed volume can be usefulfor treatment. In the case of an elliptic or cylindrical coil, theelectric field may extend beyond the edge of the coil in thelongitudinal direction. The extension of the electric field may allowpositioning of the greater portion of the subjects head outside of thecoil. Such a positioning enables the inducement of electric fieldswithin the head of a subject with a reduced risk of claustrophobia, andimproves the comfort of the subject.

Spherical Coils

As illustrated in FIGS. 8A-8C, the fields described above may beaccomplished with the use of coils that form a spherical shape ormounting surface. Spherical coils that produce the LFMS fields in theirinterior have the solutions

${{\overset{\rightarrow}{B}}_{-}\left( {\overset{\rightarrow}{r},t} \right)} = {{{G(t)}\left\{ {{\hat{r}2\; r\; \sin \; \theta \; \cos \; \theta \; \cos \; \phi} + {\hat{\theta}{r\left( {{\cos^{2}\theta} - {\sin^{2}\theta}} \right)}\cos \; \phi} - {\hat{\phi}r\; \cos \; {\theta sin}\; \phi}} \right\}} = {{G(t)}\left\{ {{\hat{r}r\; \sin \; 2\theta \; \cos \; \phi} + {\hat{\theta}r\; \cos \; 2{\theta cos}\; \phi} - {\hat{\phi}r\; \cos \; {\theta sin}\; \phi}} \right\}}}$${{\overset{\rightarrow}{B}}_{+}\left( {\overset{\rightarrow}{r},t} \right)} = {{G(t)}\left\{ {{\hat{r}\frac{R^{5}}{r^{4}}\sin \; 2\; {\theta cos}\; \phi} - {\frac{2}{3}\hat{\theta}\frac{R^{5}}{r^{4}}\cos \; 2\; \theta \; \cos \; \phi} + {\frac{2}{3}\hat{\phi}\frac{R^{5}}{r^{4}}\cos \; \theta \; \sin \; \phi}} \right\}}$${\overset{\rightarrow}{J}\left( {t,\theta,\phi} \right)} = {{- \frac{1}{\mu}}\frac{5}{3}{G(t)}R\left\{ {{\hat{\theta}\cos \; \theta \; \sin \; \phi} + {\hat{\phi}\cos \; 2\theta \; \cos \; \phi}} \right\}}$

In these equations, some of the parameters of the spherical shapeinclude the radius of the sphere, r, a polar angle of a coil segment onthe sphere, theta, and the azimuth angle of the coil segment, phi. Thenumber, size, and/or current patterns of coil elements are determinedaccording to one or more of these parameters based on the equationsabove such that a desired target field is achieved while limiting thecurrent density to an acceptable level so that the coil does notgenerate excessive heat. There are four non-overlapping current patternsin the spherical coil, and thus four coil elements, in this design. Forpractical use only half the coil with two elements disposed in azimuthmay be in use in order to accommodate human subjects efficiently. Thesetwo coil elements can be referred to as spherical coil quadrants becausethere are four elements in a full spherical coil.

Although a complete sphere cannot be used to treat a human subject'shead, a half sphere cut along the plane theta=90 can providesubstantially the same field, with somewhat less efficiency, that can becompensated for by supplying more current to the coil. The hemisphericalcoil, shown in FIG. 8B, has resemblance to the cylinder coil in that theazimuth currents follow a cos(theta) behavior. If this coil is alignedwith phi=0 to the L or R of the subjects head, a field substantially thesame as for the X gradient can be produced, with electric fields inducedin the cortex along the A-P direction. If the hemisphere is rotated sothat phi=0 is in the A or P direction, then electric fields induced inthe cortex may follow a L-R pattern cross between hemispheres. A singlequadrant element depicted in FIG. 8C may be used following the samepattern in any position in order to focus on a particular area of thecortex.

In general, a spherical coil is more comfortable to a patient as it isnot as close to the patient's head as the conventional cylindrical coilwould be. A spherical coil, however, typically needs more currentrelative to a cylindrical coil to induce an electric field of about thesame strength as that induced by a cylindrical coil. This is at least inpart because unlike while using a cylindrical coil, when using aspherical coil the patient's head is often further away from theenclosed volume of the coil. For treatment/enhancement of brain functionthe required field strength is not as high as that required for imaging,and two quadrant and single quadrant spherical coils can be used toinduce the desired electric field.

The hemispherical coil depicted in FIG. 8B has two coil elements; eachis centered at points 180 degrees apart in azimuth, and subtendssubstantially 180 degrees in its extent. A sufficient field of the samepattern may be produced if a coil element is placed centered at an angleof 0, 90, 180, or 270 degrees and subtends between 90 and 180 degrees asshown in FIGS. 8A-8C.

Coils that are focused on the PFC regions may use one or more elementsthat subtend only 45-90 degrees and that are placed less than 180degrees apart, e.g., 90 degrees apart, may be used to increaseefficiency. These coils follow the azimuth symmetry of the basic (i.e.,cylindrical) LFMS coil in that azimuth current follows a substantiallycos(phi) pattern.

Flat and Angled Coils

With reference to FIGS. 9A-9C and FIG. 10, coils providing equivalentfields may be constructed using plane and angled plane geometries. Thesame relationship between the rotations of the current densities as incylindrical coils is preserved in these coils. These coils are electriccurrent solutions of the same basic LFMS fields that have been producedon different boundaries.

Pulse Generator

The electronics module includes an amplifier, and a waveform generator.The waveform generator provides a sequence of electrical pulses (i.e.,voltage pulses) to the amplifier, which amplifies them and providescurrent pulses to the coil elements. Those current pulses typicallygenerate a magnetic field, as described above. The current required bythe coil elements may also be delivered by controlling voltage acrossthe coil leads. A voltage waveform required to produce a desired currentwaveform (i.e., a current pulse sequence) in the coil elements can becomputed based on the known impedance of the coil. In one embodiment thewaveform generator is a general-purpose programmable computer. Inanother embodiment the waveform generator is a purpose-built electriccircuit. The waveform generator is able to provide the waveformsdescribed in this specification.

In one embodiment, the electrical pulses generated by the waveformgenerator are continuous alternating trapezoid pulses. These producesimilar continuous, alternating trapezoid variation of the magneticfield generated by the coil. The corresponding induced electric fieldmay include square pulses that occur during the trapezoid ramps,alternating in sign, and with no field during the generally flatsegments of the trapezoid. In one embodiment, the electric pulsesincludes bursts of 512 trapezoids at a time, with zero-to-peak ramp timeof about 128 microseconds, and generally flat segments of the trapezoidin a duration of about 768 microseconds. There is a waiting period ofabout 1.5 seconds in between a sequence of pulses, and the treatmentlasts for approximately 20 minutes. Treatment times may be increased upto the tolerance of the subject and may be as short as 1 minute.

In one embodiment the electric field is delivered as a train ofsubstantially unipolar pulses with pulse duration in the range of 50microseconds to 10 milliseconds. The individual pulses in this train mayeither alternate, or maintain the same polarity within the pulse train.Specifically, a unipolar pulse is a pulse having continuous values thatare all either only greater than zero, or continuous values that are allonly less than zero. A single pulse does not have continuous values thatare both greater than and less than zero. Two consecutive pulses,separated by an interval of substantially zero value, may however havedifferent polarities.

A general pulse pattern is shown in FIG. 11, which shows a square pulsepattern with 3 bursts of 12 square pulses each. In one embodiment thepulses are separated by substantially no field. The pulses may havealternating polarity and may have the same absolute magnitude.

As depicted in FIG. 12, in one embodiment there are long periods ofsmall opposite sign/polarity electric field periods between the pulsesin a way that has substantially no net integral, but that continues toprovide pulsed behavior. This can be achieved by configuring the pulsegenerator such that the magnetic field 1202 rises at a first rate duringa first interval 1204. For example, the first interval 1204 is 0.25 mslong, and the magnetic field rises from about −30 Gauss up to about +30Gauss during that interval, i.e., at a rate of about 234 Gauss/ms, Then,during a second interval 1206, the pulse generator is configured suchthat the magnetic field decreases at a second, substantially smallerrate. For example, the second interval 1206 is 0.75 ms long, and themagnetic field 1202 decreases from about +30 Gauss down to about −30Gauss during that interval, i.e., at a rate of about 80 Gauss/ms, whichis substantially smaller than the rate 234 Gauss/ms. It should beunderstood that the strengths of the magnetic field and the lengths ofintervals described above are exemplary. Other embodiments may employweaker or stronger magnetic fields, e.g., −50 to +50 Gauss, −20 to +20Gauss, −20 to +50 Gauss, etc. The first interval may be shorter orlonger such as 0.1 ms, 0.2 ms, 0.5 ms, etc., and the second interval mayalso be shorter or longer such as 0.5 ms, 1 ms, etc. An electric pulse1208 having a magnitude greater than zero (e.g., 0.5 V/m, 0.7 V/m, 0.9V/m, etc.) is generated when the magnetic field rises rapidly during thefirst interval. An electric field 1210 of relatively low magnitude andnegative polarity (e.g., −0.1 V/m, −0.2 V/m, etc.) is generated duringthe second interval, and that field has the effect of providing anegative reference point for the positive pulses 1208. Integrated overthe first and second intervals 1204, 1206, the electric field has asubstantially zero integral value, i.e., no net integral. The first andsecond intervals are repeated so as to form a series of pulses separatedby relatively long periods of small opposite polarity electric fields.The frequency of these pulses is greater than about 100 Hz, andpreferably about 1 kHz.

As depicted in FIG. 13, in one embodiment the pulses are sinusoidalpulses 802 that are delivered in a first interval 1304 of continuouspulses that are separated by a second interval 1306 of no pulses,similar to the burst embodiment. In this case a burst, i.e., a periodcomprising a pair of consecutive first and second intervals 1304, 1306,has a duty cycle of less than 100%. Within the first interval, the pulsegenerator configures the gradient magnetic field such that the amplitudeof all of the sinusoidal pulses 1302 is substantially constant, e.g.,about 0.5 V/m, 0.7 V/m, 0.9 V/m, etc. The variation in the amplitude ofconsecutive pulses may be less than 0.5%, 1%, or 5%. In someembodiments, the amplitude of the sinusoidal pulses in at least one orat least two subsequent bursts is also about the same as the amplitudeof the sinusoidal pulses in the first burst. Continuous sinusoidal pulsetrains may be employed for a more efficient delivery of the basefrequency as long as the pulses are substantially identical (up to sign)in amplitude and form in order to provide a steady state stimulus. Thefrequency of the sinusoidal pulses is greater than about 100 Hz, andpreferably about 500 Hz. In comparison to a series of alternating pulsesthat are delivered at 1 kHz, a 500 Hz sine pulse train achieves the same1 ms spacing between peak electric fields as the separated pulses. Insome embodiments, the duty cycle of the burst is 100%, i.e., the secondinterval is zero seconds.

Patient Positioning for Treatment

In one embodiment the coil and coil housing are positioned such that asubject would be in a lying position. In the case of an ellipticcylinder, the longitudinal direction would be horizontal. In anotherembodiment the coil and coil housing are positioned such that a subjectwould be sitting or standing. In the case of an elliptic cylinder, thelongitudinal direction would be vertical. In another embodiment, thecoil and coil housing are positioned with the longitudinal direction atan angle between horizontal and vertical.

The patient positioning module provides assistance for the placement ofa subject for delivery of the magnetic fields. It may include: (i) aheadrest; (ii) physical markers; (iii) visual positioning markings; and(iv) lasers.

The headrest provides support to the patient's head and/or neck. Theheadrest includes a shaped material, preferably a plastic to accommodatea cushion layer upon it. The cushion layer is preferably made of foamwith a plastic, vinyl or other coating that can be easily cleaned. Theheadrest is preferably located in front of the opening of the coil orpartially within the coil.

In one embodiment physical markers are provided. The physical markersmay include rods, pins, or stereotactic frames. The physical markersprovide guidance for positioning of the subject's head in the optimalposition. For example a rod may be inserted from both the left and rightof the subject, illustrating the optimal location of an aspect of thesubject's anatomy, such as the temples.

In one embodiment visual positioning markings are provided. The visualpositioning markings may be located on the coil housing, on theheadrest. The positioning markings may include arrows, lines, or othermarkings that help align the patient's head with respect to the coil.

In one embodiment lasers are incorporated into the system. One or morelaser points, lines or cross-marks may be employed. The lasers assist inpositioning the patient's head with respect to the coil. For example,two laser lines may be employed, with one creating a line in thesagittal direction and the other creating a line in the axial direction.The intersection of these two lines would illustrate the location of aspecific part of the subject's anatomy, such that when that area ofanatomy is aligned with the lasers, the subject's head is optimallylocated with respect to the coil.

The control module allows the user of the system to control itsoperations. It includes: (i) a computer; (ii) software; (iii) a display;(iv) an input device. The software includes a user interface, controlelectronics, data acquisition and data storage functionality. The inputdevice may be one or more of: a mouse, keyboard, track pad, button,joystick, microphone for accepting voice commands, or other input deviceas is known in the art.

A method is provided for the use of the system, wherein a subject isplaced within or adjacent to the coil module, and wherein electricfields are delivered to the subject.

The system and method may be used for the treatment of psychiatricdisorders, including depression, stress and anxiety, schizophrenia,PTSD, and OCD, or for the enhancement of brain function. In treating apatient, the system may be employed to induce a single series ofelectric fields or multiple series of electric fields. Multiple seriesof electric fields may be spaced apart in time.

Clinical Trial

Sixty-three patients who met DSM-IV criteria for either bipolar disorder(BPD, N=41) or major depressive disorder (MDD, N=22) and who had a scoreof 17 or greater on the 17-item Hamilton Depression Rating Scale (HDRS)were randomized to receive either LFMS or sham treatment. Subjectsparticipating in the study (mean baseline HDRS score of 22.4±4.2) wereon a stable regimen of antidepressant or mood stabilizing medicationsfor at least 6 weeks prior to randomization. Most subjects were takingmultiple medications. This study was a double blinded, randomized,sham-controlled investigation of the acute mood effects of a single20-minute exposure to LFMS. The HDRS, the Visual Analogue Scale (VAS)and the Positive and Negative Affect Scale (PANAS) were used to assesmood and depression systems pre and post-treatment. In the VAS, thesubjects are asked to “Place an X on the line in a place that representshow your mood is at this moment [0-10]”).

The group of all subjects (n=63) showed improvement with LFMS treatmentover sham treatment in all outcome measures. These results show twoimportant results. First, the portable LFMS Device can replicate theimmediate mood improvement observed in the original study that used anMRI system. Second, the effects can be observed in subjects with MDD aswell as those with BPD

Having described certain embodiments of the invention, it will beapparent to those of ordinary skill in the art that other embodimentsincorporating the concepts disclosed herein may be used withoutdeparting from the spirit and scope of the invention. Accordingly, thedescribed embodiments are to be considered in all respects as onlyillustrative and not restrictive.

What is claimed is:
 1. A system comprising: a pulse generator; and amagnetic coil having a first element, the first element comprising (1) afirst layer having an interior surface and an exterior surface, and (2)a second layer having an interior surface and an exterior surface,wherein the interior surface of the second layer is separated from theexterior surface of the first layer by a distance, and wherein the firstand second layers are in electrical communication with the pulsegenerator and adapted to produce respective first and second magneticfields, and the first and second layers are positioned such that thefirst and second magnetic fields combine to produce an aggregatemagnetic field having a field strength greater than either the first orsecond magnetic field.
 2. The system of claim 1, wherein the distancebetween all points of the interior surface of the second layer and allcorresponding points of the exterior surface of the first layer iswithin a tolerance that is less than about 25 percent of a mediandistance between the two surfaces.
 3. The system of claim 1, wherein thedistance is less than about 5 millimeters.
 4. The system of claim 1,wherein the interior surface of the first element is either a curvedsurface or a segmented surface comprising at least two segments at anangle with respect to one another.
 5. The system of claim 1, wherein thefirst layer of the first element comprises a pattern cut in a metalsurface or wound wire.
 6. The system of claim 5, wherein the wound wirecomprises one of solid wire, stranded wire, and stranded, insulated litzwire.
 7. The system of claim 1, wherein the first layer of the firstelement comprises a plurality of turns of a conductor, at least one pairof adjacent turns being spaced apart and the plurality of turns beingdistributed over the first layer.
 8. The system of claim 1, wherein thedistance is selected such that the aggregate magnetic field is producedin a region proximate to the magnetic coil.
 9. The system of claim 8,wherein the first and second layers are configured such that each layergenerates less than about 50 W of heat.
 10. The system of claim 1,wherein the first element comprises a third layer having an interiorsurface and an exterior surface, wherein the interior surface of thethird layer is separated from the exterior surface of the second layerby a distance, and wherein the third layer produces a third magneticfield that combines with the first and second magnetic fields to producean aggregate magnetic field having a field strength greater than theaggregate magnetic field produced by the first or second magneticfields.
 11. The system of claim 1, wherein the magnetic coil comprises asecond element, an inner surface of the second element and the innersurface of the first element forming separate portions of a singlesurface.
 12. The system of claim 11, wherein: the single surface is theouter surface of a cylinder having a diameter of about 14 inches; thesecond element comprises two layers; and each of the first and secondlayers of the first element, and each of the two layers of the secondelement comprises a spiral pattern.
 13. A method of treating apsychiatric disorder or enhancing brain function using the system ofclaim 1, the method comprising: supplying electric power to the magneticcoil via the pulse generator to produce the aggregate magnetic field,and thereby inducing an electric field in air proximate to the coil; anddisposing a subject relative to the magnetic coil such that at least aportion of the subject's head is located in a region where the electricfield is induced.
 14. The method of claim 13, wherein the psychiatricdisorder comprises at least one of mood disorder, depression, stress andanxiety, schizophrenia, PTSD, and OCD.
 15. The method of claim 13,wherein a position in which the subject is disposed is either a supineposition or a seated position.
 16. A system comprising: a pulsegenerator; and a magnetic coil comprising a first element, an innersurface of the first element forming at least a part of a sphericalsurface, the first element being in electrical communication with thepulse generator.
 17. The system of claim 16, wherein a parameter of themagnetic coil is selected such that the coil produces a gradientmagnetic field proximate to a region at least partially enclosed by thespherical surface, the gradient magnetic field inducing an electricfield in air up to about 50 V/m.
 18. The system of claim 17, wherein theparameter is selected from the group consisting of a radius of thespherical surface, a polar angle of a coil segment, and an azimuth angleof the coil segment.
 19. The system of claim 16, wherein the magneticcoil comprises a second element, an inner surface of the second elementand the inner surface of the first element forming separate portions ofthe spherical surface.
 20. The system of claim 16, wherein the firstelement comprises a first layer having an interior surface and anexterior surface, and a second layer having an interior surface and anexterior surface, wherein the interior surface of the second layer isseparated from the exterior surface of the first layer by a distance.21. The system of claim 20, wherein the distance between all points ofthe interior surface of the second layer and all corresponding points ofthe exterior surface of the first layer is within a tolerance that isless than about 25 percent of a median distance between the twosurfaces.
 22. The system of claim 16, wherein the first elementcomprises a plurality of turns of a conductor, at least one pair ofadjacent turns being spaced apart and the plurality of turns beingdistributed over the first element.
 23. A method of treating apsychiatric disorder or enhancing brain function using the system ofclaim 16, the method comprising: supplying electric power to themagnetic coil via the pulse generator to produce a gradient magneticfield proximate to a region at least partially enclosed by the sphericalsurface, thereby inducing an electric field in air proximate to thecoil; and disposing a subject relative to the magnetic coil such that atleast a portion of the subject's head is located in a region where theelectric field is induced.
 24. The method of claim 23, wherein thepsychiatric disorder comprises at least one of mood disorder,depression, stress and anxiety, schizophrenia, PTSD, and OCD.
 25. Themethod of claim 23, wherein a position in which the subject is disposedis either a supine position or a seated position.
 26. A method oftreatment using an induced electric field, the method comprising thesteps of: (a) controlling a pulse generator during a first interval toproduce a gradient magnetic field using a coil, the magnetic fieldhaving a magnitude that increases at a first rate during the firstinterval; (b) controlling the pulse generator during a second intervalthat is substantially longer than the first interval, such that themagnitude of the magnetic field decreases during the second interval ata second rate substantially smaller than the first rate, such that anelectric field having a magnitude greater than zero is induced in airduring the first interval and an electric field of a negative magnitudeis induced in air during the second interval, wherein an electric fieldintegrated over a period comprising the first and second intervals issubstantially zero; (c) repeating alternately steps (a) and (b); and (d)disposing a subject relative to the coil such that at least a portion ofthe subject's head is located in a region where the electric field isinduced.
 27. The method of claim 26, wherein a repetition of theelectric field having a magnitude greater than zero forms a series ofelectric field pulses having a frequency of at least 100 Hz.
 28. Themethod of claim 26, wherein the portion of the subject's brain comprisesat least a portion of cortical surface of the subject's brain.
 29. Themethod of claim 26, wherein the treatment comprises enhancing brainfunction or treating a psychiatric disorder, the psychiatric disordercomprising at least one of mood disorder, depression, stress andanxiety, schizophrenia, PTSD, and OCD.
 30. The method of claim 26,wherein a position in which the subject is disposed is either a supineposition or a seated position.
 31. A method of treatment using aninduced electric field, the method comprising the steps of: (a)controlling a pulse generator during a first interval to produce agradient magnetic field using a coil, wherein the gradient magneticfield induces a plurality of consecutive sinusoidal electrical pulseshaving substantially constant amplitude in air during the firstinterval; (b) controlling the pulse generator during a second intervalsuch that the gradient magnetic field induces an electric field ofsubstantially zero magnitude in air during the second interval; (c)repeating alternately the steps (a) and (b); and (d) disposing a subjectrelative to the coil such that at least a portion of the subject's headis located in a region where the plurality of sinusoidal pulses isinduced.
 32. The method of claim 31, wherein a frequency of theconsecutive sinusoidal pulses is greater than about 100 Hz.
 33. Themethod of claim 31, wherein the portion of the subject's brain comprisesat least a portion of cortical surface of the subject's brain.
 34. Themethod of claim 31, wherein the treatment comprises enhancing brainfunction or treating a psychiatric disorder, the psychiatric disordercomprising at least one of mood disorder, depression, stress andanxiety, schizophrenia, PTSD, and OCD.
 35. The method of claim 31,wherein a position in which the subject is disposed is either a supineposition or a seated position.